CELLS OF THE IMMUNE SYSTEM

Dr. Rojan Ghanim AL-allaff

Reading: Coico and Sunshine. Immunology: A Short Course. John Wiley & Sons, Inc, New
York,NY. 6th edition, 2009. Chapter 2; Geha and Notarangelo. Case Studies in Immunology.
Garland Publishing, New York, NY. 6th edition, 2012. Case 30: Congenital Asplenia.
Web Resource:
http://www.uth.tmc.edu/pathology/medic/immunology/Immuno/cellsimmsys.html

Immune system cells are derived from pluripotent hematopoietic stem cells in the bone
marrow.These cells can be functionally divided into groups that are involved in two major
categories of immune responses: innate (natural) and acquired. Innate immunity is present
from birth and consists of non-specific components. Acquired immunity by definition
requires recognition specificity to foreign (non-self) substances. The major properties of the
acquired immune response are specificity, memory, adaptiveness, and discrimination between
self and non-self.
The acquired immune response is subdivided into humoral and cellular immunity, based on
participation of two major cell types. In Humoral Immunity, B lymphocytes synthesize and
secrete antibodies.Cellular Immunity (CMI) involves effector T lymphocytes which secrete
immunoregulatory factors following interaction with antigen presenting cells (APCs).

Leukocytes

Leukocytes provide either innate or specific adaptive immunity. These cells are derived from
myeloid or lymphoid lineage. Myeloid cells include highly phagocytic, motile neutrophils,
monocytes, and macrophages that provide a first line of defense against most pathogens. The
other myeloid cells, including eosinophils, basophils, and their tissue counterparts, mast cells,
are involved in defense against parasites and in the genesis of allergic reactions. Cells from
the lymphoid lineage are responsible for humoral or cell mediated immunity.

Myeloid Cells

Neutrophils: Neutrophils are the most highly adherent, motile, phagocytic leukocytes and
are the first cells recruited to acute inflammatory sites. They ingest, kill, and digest
pathogens, with their functions dependent upon special proteins, such as adherence
molecules, or via biochemical pathways (respiratory burst).

Eosinophils: Eosinophils defend against parasites and participate in hypersensitivity

reactions via cytotoxicity. Their cytotoxicity is mediated by large cytoplasmic granules,
which contain eosinophilic basic and cationic proteins.

Basophils/Mast cells: Basophils, and their tissue counterpart mast cells, produce cytokines
that help defend against parasites, and also cause allergic inflammation. These cells display
high affinity surface membrane receptors for IgE antibodies, and have many cytoplasmic
granules containing heparin and histamine. The cells degranulate when cell-bound IgE
antibodies are crosslinked by antigens, and produce low-molecular weight vasoactive
mediators (e.g. histamine).
Monocytes/Macrophages:Monocytes and macrophages are involved in phagocytosis and
intracellular killing of microorganisms.Macrophages are differentiated monocytes,which are
one of the principal cells found to reside for long periods in the RES reticulo-endothelial
system. These monocytes/macrophages are highly adherent, motile and phagocytic; they
marshal and regulate other cells of the immune system, such as T lymphocytes; they serve as
antigen processing-presenting cells.

Dendritic Cells: Dendritic cells provide a link between innate and adaptive immunity by
interacting with T cells in a manner to deliver strong signals for development of memory
responses. Dendritic cells recognize foreign agents and pathogens through a series of pattern
recognition receptors (non-specific), and are able to present antigen to both T helper and T
cytotoxic cells to allow those lymphocytes to mature towards functionality.

Lymphoid Cells

Lymphoid cells provide efficient, specific and long-lasting immunity against

microbes/pathogens and are responsible for acquired immunity. Lymphocytes differentiate
into three separate lines: (1)thymic-dependent cells or T lymphocytes that operate in cellular
and humoral immunity; (2) B-lymphocytes that differentiate into plasma cells to secrete
antibodies; and (3) natural killer (NK) cells. T and B lymphocytes produce and express
specific receptors for antigens while NK cells do not.

B Lymphocytes: B lymphocytes differentiate into plasma cells to secrete antibodies. The

genesis of mature B cells from pre-B cells is antigen-independent. The activation of B cells
into antibody producing/secreting cells (plasma cells) is antigen-dependent. Mature B cells
can have 1-1.5 x 105 receptors for antigen embedded within their plasma membrane. Once
specific antigen binds to surface Ig molecule, the B cells differentiate into plasma cells that
produce and secrete antibodies of the same antigen-binding specificity. If B cells also interact
with T helper cells, they proliferate and switch the isotype (class) of immunoglobulin that is
produced, while retaining the same antigen-binding specificity. T helper cells are thought to
be required for switching from IgM to IgG, IgA, or IgE isotypes. In addition to antibody
formation, B cells also process and present protein antigens.

T Lymphocytes: T lymphocytes are involved in the regulation of the immune response and
in cell mediated immunity, and help B cells to produce antibody. Mature T cells express
antigen-specific T cell receptors (TCR). Every mature T cell also expresses the CD3
molecule, which is associated with the TCR. In addition mature T cells usually display one
of two accessory molecules, CD4 or CD8, which define whether a T cell will be a helper T
lymphocyte, or a cytotoxic T lymphocyte (CTL). The TCR/CD3 complex recognizes antigens
associated with the major histocompatibility complex (MHC) molecules on target cells (e.g.
virus-infected cell).

1- T Helper Cells: T helper cells (Th) are the primary regulators of T cell- and B cell-
mediated responses. They 1) aid antigen-stimulated subsets of B lymphocytes to
proliferate and differentiate toward antibody-producing cells; 2) express the CD4
molecule; 3) recognize foreign antigen complexed with MHC class II molecules on B
 cells, macrophages or other antigen-presenting cells; and 4) aid effector T lymphocytes
in cell-mediated immunity.
2- Cytotoxic T Cells: T cytotoxic cells (CTLs) are cytotoxic against tumor cells and host
cells infected with intracellular pathogens. These cells 1) usually express CD8, and, 2)
destroy infected cells in an antigen-specific manner that is dependent upon the
expression of MHC class I molecules on antigen presenting cells.
3- T Suppressor/ T Regulatory Cells: T suppressor cells suppress the T and B cell
responses and express CD8 molecules. T regulatory cells (Tregs) also affect T cell
response, with many cells characterized as CD4+CD25+, TGF- secretors. Tregs
regulate/suppress other T cell activities, and help prevent development of autoimmunity.
4- Natural Killer T Cells: Natural killer T cells (NKT) are a heterogeneous group of T
cells that share properties of both T cells and natural killer (NK) cells. These cells were
identified as T cells that recognize an antigen-presenting molecule (CD1d) able to bind
self- and foreign lipids and glycolipids. They constitute only 0.2% of all peripheral blood
T cells. The term “NK T cells” was first used in mice to define a subset of T cells that
expressed the natural killer (NK) cell-associated marker NK1.1 (CD161). It is now
generally accepted that the term “NKT cells” primarily refer to CD1d-restricted T cells
co-expressing a heavily biased, semi-invariant T cell receptor (TCR) and NK cell
markers. Natural killer T (NKT) cells should not be confused with natural killer (NK
cells).
Natural Killer Cells: NK cells are large granular “innate” lymphocytes that nonspecifically
kill certain types of tumor cells and virus-infected cells. NK cells share many surface
molecules with T lymphocytes. These circulating large granular lymphocytes are able to kill
“self” in the absence of antigen-specific receptors. NK cells are especially effective against
viral infected cells, and keep the expansion of virus in check until adaptive immunity kicks
in. In this regard, they also secrete interferon-gamma, which is an effective immunoregulator.
NK cells can also kill via antibody-dependent cellular cytotoxic mechanisms (ADCC) via
their Fc receptors. NK cells express a large number of receptors that deliver either activating
or inhibitory signals, and the relative balance of these signals controls NK cell activity.
Figure. The developmental pathway of pluripotent bone marrow stem cells.
Coico and Sunshine, 2009. Fig. 2.1.